Reliable differentiation of necrosis and active metabolically contours of glioblastoma multiforme using susceptibility-based imaging.

Purpose: Gadolinium-enhancing necrosis in glioblastoma multiforme (GBM), as an occasionally occurring false positive in contrast enhancement (CE) imaging, leads to trouble for segmentation of GBM and treatment. Therefore, the investigation of complementary detection way to identify the metabolically active volume of the tumor with high reliability is very worth to be addressed. Here, we reported on a case of GBM with gadolinium-enhancing necrosis in an experimental CE imaging study in mice and evaluated the discrimination of the necrosis and metabolically active parts of the GBM using conventional and state-of-the-art susceptibility-based MRI. Methods: In this study, following 5-aminolevulinic acid (ALA) and iron supplements (FAC, 6 h after ALA, intra-tumoral injection) to animal, T2*-W imaging and quantitative susceptibility mapping (QSM) were performed, and compared with CE imaging. Results: The signal intensity (SI) of the active and necrosis areas of the case in the CE image demonstrated no significant difference while the SI on the T2*-W images and susceptibility value in QSM changed 24 and 150%, respectively. Conclusion: The preclinical case report provides valuable insights into the potential of susceptibility-based MRI using ALA + FAC to apply as a robust discriminator between necrotic and viable tumors.

The diamagnetic component map from quantitative susceptibility mapping (QSM) source separation reveals pathological alteration in Alzheimer's disease-driven neurodegeneration.

A sensitive and accurate imaging technique capable of tracking the disease progression of Alzheimer's Disease (AD) driven amnestic dementia would be beneficial. A currently available method for pathology detection in AD with high accuracy is Positron Emission Tomography (PET) imaging, despite certain limitations such as low spatial resolution, off-targeting error, and radiation exposure. Non-invasive MRI scanning with quantitative magnetic susceptibility measurements can be used as a complementary tool. To date, quantitative susceptibility mapping (QSM) has widely been used in tracking deep gray matter iron accumulation in AD. The present work proposes that by compartmentalizing quantitative susceptibility into paramagnetic and diamagnetic components, more holistic information about AD pathogenesis can be acquired. Particularly, diamagnetic component susceptibility (DCS) can be a powerful indicator for tracking protein accumulation in the gray matter (GM), demyelination in the white matter (WM), and relevant changes in the cerebrospinal fluid (CSF). In the current work, voxel-wise group analysis of the WM and the CSF regions show significantly lower |DCS| (the absolute value of DCS) value for amnestic dementia patients compared to healthy controls. Additionally, |DCS| and τ PET standardized uptake value ratio (SUVr) were found to be associated in several GM regions typically affected by τ deposition in AD. Therefore, we propose that the separated diamagnetic susceptibility can be used to track pathological neurodegeneration in different tissue types and regions of the brain. With the initial evidence, we believe the usage of compartmentalized susceptibility demonstrates substantive potential as an MRI-based technique for tracking AD-driven neurodegeneration.

Aberrant dentato-rubro-thalamic pathway in action tremor but not rest tremor: A multi-modality magnetic resonance imaging study.

AIMS: The purpose of this study was to clarify the dentato-rubro-thalamic (DRT) pathway in action tremor in comparison to normal controls (NC) and disease controls (i.e., rest tremor) by using multi-modality magnetic resonance imaging (MRI). METHODS: This study included 40 essential tremor (ET) patients, 57 Parkinson's disease (PD) patients (29 with rest tremor, 28 without rest tremor), and 41 NC. We used multi-modality MRI to comprehensively assess major nuclei and fiber tracts of the DRT pathway, which included decussating DRT tract (d-DRTT) and non-decussating DRT tract (nd-DRTT), and compared the differences in DRT pathway components between action and rest tremor. RESULTS: Bilateral dentate nucleus (DN) in the ET group had excessive iron deposition compared with the NC group. Compared with the NC group, significantly decreased mean diffusivity and radial diffusivity were observed in the left nd-DRTT in the ET group, which were negatively correlated with tremor severity. No significant difference in each component of the DRT pathway was observed between the PD subgroup or the PD and NC. CONCLUSION: Aberrant changes in the DRT pathway may be specific to action tremor and were indicating that action tremor may be related to pathological overactivation of the DRT pathway.

Quantitative susceptibility mapping shows lower brain iron content in children with childhood epilepsy with centrotemporal spikes.

PURPOSE: The dysregulation of brain iron homeostasis is closely relevant to a multitude of chronic neurological disorders. This study employed quantitative susceptibility mapping (QSM) to detect and compare whole-brain iron content between childhood epilepsy with centrotemporal spikes (CECTS) children and typically developing children. MATERIALS AND METHODS: 32 children with CECTS and 25 age- and gender-matched healthy children were enrolled. All participants were imaged with 3.0-T MRI to acquire the structural and susceptibility-weighted data. The susceptibility-weighted data were processed using STISuite toolbox to obtain QSM. The magnetic susceptibility difference between the two groups was compared using voxel-wise and region of interest methods. Multivariable linear regression, controlling for age, were employed to investigate the associations between the brain magnetic susceptibility and age at onset. RESULTS: Lower magnetic susceptibility was mainly observed in sensory- and motor-related brain regions in children with CECTS, including bilateral middle frontal gyrus, supplementary motor area, midcingulate cortex, paracentral lobule and precentral gyrus, the magnetic susceptibility of right paracentral lobule, right precuneus and left supplementary motor area were found to have positive correlation with the age at onset. CONCLUSIONS: This study suggests that the potential iron deficiency in certain brain regions is associated with CECTS, which might be helpful for further illumination of potential pathogenesis mechanism of CECTS.

Spatial patterns of elevated magnetic susceptibility in progressive apraxia of speech.

PURPOSE: Progressive apraxia of speech (PAOS) is a neurodegenerative disorder affecting the planning or programming of speech. Little is known about its magnetic susceptibility profiles indicative of biological processes such as iron deposition and demyelination. This study aims to clarify (1) the pattern of susceptibility in PAOS patients, (2) the susceptibility differences between the phonetic (characterized by predominance of distorted sound substitutions and additions) and prosodic (characterized by predominance of slow speech rate and segmentation) subtypes of PAOS, and (3) the relationships between susceptibility and symptom severity. METHODS: Twenty patients with PAOS (nine phonetic and eleven prosodic subtypes) were prospectively recruited and underwent a 3 Tesla MRI scan. They also underwent detailed speech, language, and neurological evaluations. Quantitative susceptibility maps (QSM) were reconstructed from multi-echo gradient echo MRI images. Region of interest analysis was conducted to estimate susceptibility coefficients in several subcortical and frontal regions. We compared susceptibility values between PAOS and an age-matched control group and performed a correlation analysis between susceptibilities and an apraxia of speech rating scale (ASRS) phonetic and prosodic feature ratings. RESULTS: The magnetic susceptibility of PAOS was statistically greater than that of controls in subcortical regions (left putamen, left red nucleus, and right dentate nucleus) (p < 0.01, also survived FDR correction) and in the left white-matter precentral gyrus (p < 0.05, but not survived FDR correction). The prosodic patients showed greater susceptibilities than controls in these subcortical and precentral regions. The susceptibility in the left red nucleus and in the left precentral gyrus correlated with the prosodic sub-score of the ASRS. CONCLUSION: Magnetic susceptibility in PAOS patients was greater than controls mainly in the subcortical regions. While larger samples are needed before QSM is considered ready for clinical differential diagnosis, the present study contributes to our understanding of magnetic susceptibility changes and the pathophysiology of PAOS.

Quantitative susceptibility mapping of basal ganglia iron is associated with cognitive and motor functions that distinguish spinocerebellar ataxia type 6 and type 3.

Background: In spinocerebellar ataxia type 3 (SCA3), volume loss has been reported in the basal ganglia, an iron-rich brain region, but iron content has not been examined. Recent studies have reported that patients with SCA6 have markedly decreased iron content in the cerebellar dentate, coupled with severe volume loss. Changing brain iron levels can disrupt cognitive and motor functions, yet this has not been examined in the SCAs, a disease in which iron-rich regions are affected. Methods: In the present study, we used quantitative susceptibility mapping (QSM) to measure tissue magnetic susceptibility (indicating iron concentration), structural volume, and normalized susceptibility mass (indicating iron content) in the cerebellar dentate and basal ganglia in people with SCA3 (n = 10) and SCA6 (n = 6) and healthy controls (n = 9). Data were acquired using a 7T Philips MRI scanner. Supplemental measures assessed motor, cognitive, and mood domains. Results: Putamen volume was lower in both SCA groups relative to controls, replicating prior findings. Dentate susceptibility mass and volume in SCA6 was lower than in SCA3 or controls, also replicating prior findings. The novel finding was that higher basal ganglia susceptibility mass in SCA6 correlated with lower cognitive performance and greater motor impairment, an association that was not observed in SCA3. Cerebellar dentate susceptibility mass, however, had the opposite relationship with cognition and motor function in SCA6, suggesting that, as dentate iron is depleted, it relocated to the basal ganglia, which contributed to cognitive and motor decline. By contrast, basal ganglia volume loss, rather than iron content, appeared to drive changes in motor function in SCA3. Conclusion: The associations of higher basal ganglia iron with lower motor and cognitive function in SCA6 but not in SCA3 suggest the potential for using brain iron deposition profiles beyond the cerebellar dentate to assess disease states within the cerebellar ataxias. Moreover, the role of the basal ganglia deserves greater attention as a contributor to pathologic and phenotypic changes associated with SCA.

Motor cortical patterns of upper motor neuron pathology in amyotrophic lateral sclerosis: A 3 T MRI study with iron-sensitive sequences.

BACKGROUND: Patterns of initiation and propagation of disease in Amyotrophic Lateral Sclerosis (ALS) are still partly unknown. Single or multiple foci of neurodegeneration followed by disease diffusion to contiguous or connected regions have been proposed as mechanisms underlying symptom occurrence. Here, we investigated cortical patterns of upper motor neuron (UMN) pathology in ALS using iron-sensitive MR imaging. METHODS: Signal intensity and magnetic susceptibility of the primary motor cortex (M1), which are associated with clinical UMN burden and neuroinflammation, were assessed in 78 ALS patients using respectively T2*-weighted images and Quantitative Susceptibility Maps. The signal intensity of the whole M1 and each of its functional regions was rated as normal or reduced, and the magnetic susceptibility of each M1 region was measured. RESULTS: The highest frequencies of T2* hypointensity were found in M1 regions associated with the body sites of symptom onset. Homologous M1 regions were both hypointense in 80-93 % of patients with cortical abnormalities, and magnetic susceptibility values measured in homologous M1 regions were strongly correlated with each other (ρ = 0.88; p < 0.0001). In some cases, the T2* hypointensity was detectable in two non-contiguous M1 regions but spared the cortex in between. CONCLUSIONS: M1 regions associated with the body site of onset are frequently affected at imaging. The simultaneous involvement of both homologous M1 regions is frequent, followed by that of adjacent regions; the affection of non-contiguous regions, instead, seems rare. This type of cortical involvement suggests the interhemispheric connections as one of the preferential paths for the UMN pathology diffusion in ALS.

Detection of glioblastoma multiforme using quantitative molecular magnetic resonance imaging based on 5-aminolevulinic acid: in vitro and in vivo studies.

OBJECTIVES: We demonstrated a novel metabolic method based on sequential administration of 5-aminolevulinic acid (ALA) and iron supplement, and ferric ammonium citrate (FAC), for glioblastoma multiforme (GBM) detection using R2' and quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: Intra-cellular iron accumulation in glioblastoma cells treated with ALA and/or FAC was measured. Cell phantoms containing glioblastoma cells and Wistar rats bearing C6 glioblastoma were imaged using a 3 T MRI scanner after sequential administration of ALA and FAC. The relaxivity and QSM analysis were performed on the images. RESULTS: The intra-cellular iron deposition was significantly higher in the glioma cells with sequential treatment of ALA and FAC for 6 h compared to those treated with the controls. The relaxivity and magnetic susceptibility values of the glioblastoma cells and rat brain tumors treated with ALA + FAC (115 ± 5 s-1 for R2', and 0.1 ± 0.02 ppm for magnetic susceptibility) were significantly higher than those treated with the controls (55 ± 18 (FAC), 45 ± 15 (ALA) s-1 for R2', p < 0.05, and 0.03 ± 0.03 (FAC), 0.02 ± 0.02 (ALA) ppm for magnetic susceptibility, p < 0.05). DISCUSSION: Sequential administration of ALA and iron supplements increases the iron deposition in glioblastoma cells, enabling clinical 3 T MRI to detect GBM using R2' or QSM.

A novel phantom with dia- and paramagnetic substructure for quantitative susceptibility mapping and relaxometry.

PURPOSE: A phantom is presented in this study that allows for an experimental evaluation of QSM reconstruction algorithms. The phantom contains susceptibility producing particles with dia- and paramagnetic properties embedded in an MRI visible medium and is suitable to assess the performance of algorithms that attempt to separate isotropic dia- and paramagnetic susceptibility at the sub-voxel level. METHODS: The phantom was built from calcium carbonate (diamagnetic) and tungsten carbide particles (paramagnetic) embedded in gelatin and surrounded by agarose gel. Different mass fractions and mixing ratios of both susceptibility sources were used. Gradient echo data were acquired at 1.5 T, 3 T and 7 T. Susceptibility maps were calculated using the MEDI toolbox and relaxation rates ΔR2∗ were determined using exponential fitting. RESULTS: Relaxation rates as well as susceptibility values generally coincide with the theoretical values for particles fulfilling the assumptions of the the static dephasing regime with stronger deviations for relaxation rates at higher field strength and for high susceptibility values. MRI raw data are available for free academic use as supplementary material. CONCLUSIONS: In this study, a susceptibility phantom is presented that might find its application in the development and quantitative validation of current and future QSM reconstruction algorithms which aim to separate the influence of isotropic dia- and paramagnetic substructure in quantitative susceptibility mapping.

Quantitative susceptibility mapping in the thalamus and basal ganglia of systemic lupus erythematosus patients with neuropsychiatric complaints.

Systemic lupus erythematosus (SLE) is an auto-immune disease characterized by multi-organ involvement. Although uncommon, central nervous system involvement in SLE, termed neuropsychiatric SLE (NPSLE), is not an exception. Current knowledge on underlying pathogenic mechanisms is incomplete, however, neuroinflammation is thought to play a critical role. Evidence from neurodegenerative diseases and multiple sclerosis suggests that neuroinflammation is correlated with brain iron accumulation, making quantitative susceptibility mapping (QSM) a potential hallmark for neuroinflammation in vivo. This study assessed susceptibility values of the thalamus and basal ganglia in (NP)SLE patients and further investigated the in vivo findings with histological analyses of postmortem brain tissue derived from SLE patients. We used a 3T MRI scanner to acquire single-echo T2*-weighted images of 44 SLE patients and 20 age-matched healthy controls. Of the 44 patients with SLE, all had neuropsychiatric complaints, of which 29 were classified as non-NPSLE and 15 as NPSLE (seven as inflammatory NPSLE and eight as ischemic NPSLE). Mean susceptibility values of the thalamus, caudate nucleus, putamen, and globus pallidus were calculated. Formalin-fixed paraffin-embedded post-mortem brain tissue including the putamen and globus pallidus of three additional SLE patients was obtained and stained for iron, microglia and astrocytes. Susceptibility values of SLE patients and age-matched controls showed that iron levels in the thalamus and basal ganglia were not changed due to the disease. No subgroup of SLE showed higher susceptibility values. No correlation was found with disease activity or damage due to SLE. Histological examination of the post-mortem brain showed no increased iron accumulation. Our results suggest that neuroinflammation in NPSLE does not necessarily go hand in hand with iron accumulation, and that the inflammatory pathomechanism in SLE may differ from the one observed in neurodegenerative diseases and in multiple sclerosis.

Imaging iron and neuromelanin simultaneously using a single 3D gradient echo magnetization transfer sequence: Combining neuromelanin, iron and the nigrosome-1 sign as complementary imaging biomarkers in early stage Parkinson's disease.

Diagnosing early stage Parkinson's disease (PD) is still a clinical challenge. Previous studies using iron, neuromelanin (NM) or the Nigrosome-1 (N1) sign in the substantia nigra (SN) by themselves have been unable to provide sufficiently high diagnostic performance for these methods to be adopted clinically. Our goal in this study was to extract the NM complex volume, iron content and volume representing the entire SN, and the N1 sign as potential complementary imaging biomarkers using a single 3D magnetization transfer contrast (MTC) gradient echo sequence and to evaluate their diagnostic performance and clinical correlations in early stage PD. A total of 40 early stage idiopathic PD subjects and 40 age- and sex-matched healthy controls (HCs) were imaged at 3T. NM boundaries (representing the SN pars compacta (SNpc) and parabrachial pigmented nucleus) and iron boundaries representing the total SN (SNpc and SN pars reticulata) were determined semi-automatically using a dynamic programming (DP) boundary detection algorithm. Receiver operating characteristic analyses were performed to evaluate the utility of these imaging biomarkers in diagnosing early stage PD. A correlation analysis was used to study the relationship between these imaging measures and the clinical scales. We also introduced the concept of NM and total iron overlap volumes to demonstrate the loss of NM relative to the iron containing SN. Furthermore, all 80 cases were evaluated for the N1 sign independently. The NM and SN volumes were lower while the iron content was higher in the SN for PD subjects compared to HCs. Interestingly, the PD subjects with bilateral loss of the N1 sign had the highest iron content. The area under the curve (AUC) values for the average of both hemispheres for single measures were: .960 for NM complex volume; .788 for total SN volume; .740 for SN iron content and .891 for the N1 sign. Combining NM complex volume with each of the following measures through binary logistic regression led to AUC values for the averaged right and left sides of: .976 for total iron content; .969 for total SN volume, .965 for overlap volume and .983 for the N1 sign. We found a negative correlation between SN volume and UPDRS-III (R2 = .22, p = .002). While the N1 sign performed well, it does not contain any information about iron content or NM quantitatively, therefore, marrying this sign with the NM and iron measures provides a better physiological explanation of what is happening when the N1 sign disappears in PD subjects. In summary, the combination of NM complex volume, SN volume, iron content and the N1 sign as derived from a single MTC sequence provides complementary information for understanding and diagnosing early stage PD.

Quantitative susceptibility-weighted imaging in amyotrophic lateral sclerosis with 3.0 T magnetic resonance imaging.

OBJECTIVE: To evaluate alterations in phase-shift values in the gray matter of patients with amyotrophic lateral sclerosis (ALS) using susceptibility-weighted imaging (SWI). METHODS: Twenty patients with definite or probable ALS and 19 age- and sex-matched healthy controls were enrolled. SWI was performed using a 3.0 T magnetic resonance imaging scanner. Phase-shift values were measured in corrected phase images using regions of interest, which were placed on the bilateral precentral gyrus, frontal cortex, caudate nucleus, globus pallidus, and putamen. RESULTS: Phase-shift values of the precentral gyrus were significantly lower in ALS patients (-0.176 ± 0.050) than in the control group (-0.119 ± 0.016) on SWI. The average phase-shift values of the frontal cortex, caudate nucleus, globus pallidus, and putamen in ALS patients (-0.089 ± 0.023, -0.065 ± 0.016, -0.336 ± 0.191, and -0.227 ± 0.101, respectively) were not significantly different from those in the healthy controls (-0.885 ± 0.015, -0.079 ± 0.018, -0.329 ± 0.136, and -0.229 ± 0.083, respectively). CONCLUSIONS: Compared with healthy controls, ALS patients had a lower phase-shift value in the precentral gyrus, which may be related to abnormal iron overload. Thus, SWI is a potential method for identifying ALS patients.

Decreasing brain iron in multiple sclerosis: The difference between concentration and content in iron MRI.

Increased brain iron concentration is often reported concurrently with disease development in multiple sclerosis (MS) and other neurodegenerative diseases. However, it is unclear whether the higher iron concentration in patients stems from an influx of iron into the tissue or a relative reduction in tissue compartments without much iron. By taking into account structural volume, we investigated tissue iron content in the deep gray matter (DGM) over 2 years, and compared findings to previously reported changes in iron concentration. 120 MS patients and 40 age- and sex-matched healthy controls were included. Clinical testing and MRI were performed both at baseline and after 2 years. Overall, iron content was calculated from structural MRI and quantitative susceptibility mapping in the thalamus, caudate, putamen, and globus pallidus. MS patients had significantly lower iron content than controls in the thalamus, with progressive MS patients demonstrating lower iron content than relapsing-remitting patients. Over 2 years, iron content decreased in the DGM of patients with MS, while it tended to increase or remain stable among controls. In the thalamus, decreasing iron content over 2 years was associated with disability progression. Our study showed that temporally increasing magnetic susceptibility in MS should not be considered as evidence for iron influx because it may be explained, at least partially, by disease-related atrophy. Declining DGM iron content suggests that, contrary to the current understanding, iron is being removed from the DGM in patients with MS.

Methods for quantitative susceptibility and R2* mapping in whole post-mortem brains at 7T applied to amyotrophic lateral sclerosis.

Susceptibility weighted magnetic resonance imaging (MRI) is sensitive to the local concentration of iron and myelin. Here, we describe a robust image processing pipeline for quantitative susceptibility mapping (QSM) and R2* mapping of fixed post-mortem, whole-brain data. Using this pipeline, we compare the resulting quantitative maps in brains from patients with amyotrophic lateral sclerosis (ALS) and controls, with validation against iron and myelin histology. Twelve post-mortem brains were scanned with a multi-echo gradient echo sequence at 7T, from which susceptibility and R2* maps were generated. Semi-quantitative histological analysis for ferritin (the principal iron storage protein) and myelin proteolipid protein was performed in the primary motor, anterior cingulate and visual cortices. Magnetic susceptibility and R2* values in primary motor cortex were higher in ALS compared to control brains. Magnetic susceptibility and R2* showed positive correlations with both myelin and ferritin estimates from histology. Four out of nine ALS brains exhibited clearly visible hyperintense susceptibility and R2* values in the primary motor cortex. Our results demonstrate the potential for MRI-histology studies in whole, fixed post-mortem brains to investigate the biophysical source of susceptibility weighted MRI signals in neurodegenerative diseases like ALS.

Investigation of quantitative susceptibility mapping in diagnosis of tuberous sclerosis complex and assessment of associated brain injuries at 1.5 Tesla.

BACKGROUND AND AIM: Tuberous sclerosis complex (TSC) is a rare disease with serious clinical consequences such as mental deficiency and epilepsy. The pathological changes of TSC include demyelination and subependymal calcified nodules. Quantitative susceptibility mapping (QSM) is a newly developed imaging technique which is capable of quantitatively measuring the susceptibility induced by iron deposition, calcification, and demyelination. The aim of this study was to investigate the use of QSM in detecting the subependymal nodules and assessing brain tissue injuries induced by cortical/subcortical tubers in TSC patients. MATERIALS AND METHODS: Twelve clinically confirmed TSC patients and fifteen gender- and age-matched healthy subjects underwent measurement with conventional magnetic resonance imaging (MRI) sequences, diffusion tensor imaging (DTI), and QSM. The TSC patients further underwent a computed tomography (CT) scan. Considering CT as the ground truth, the detection rates of subependymal nodules using conventional MRI and QSM were compared by the paired Chi-square test, and the sensitivity and specificity were computed. The Bland-Altman test and independent t-test were performed to compare the susceptibility of cortical/subcortical regions from QSM and fractional anisotropy (FA) values from DTI between the patient and control groups, Pearson correlation was performed to examine the correlation between the susceptibility and FA values. RESULTS: QSM was better in detecting subependymal calcified nodules compared to conventional MR sequences (X 2=40.18, P<0.001), QSM achieved a significantly higher sensitivity of 98.3% and a lower specificity of 50%, which was compared with conventional MR sequences (46.7% and 75%, respectively). The susceptibility value of cortical/subcortical tubers in TSC patients was significantly higher than those in the control group (t=9.855, P<0.001), while FA value was lower (t=-8.687, P<0.001). Pearson correlation test revealed a negative correlation between susceptibility and FA values in all participants (r=-0.65, P<0.001). CONCLUSIONS: QSM had a similar ability in TSC compared to CT and DTI. QSM may provide valuable complementary information to conventional MRI imaging and may simplicity imaging of patients with TSC. RELEVANCE FOR PATIENTS: This study shows the feasibility of QSM to detect subependymal calcified nodules. It may provide quantitative information of white matter damage of tuberous sclerosis patients.

Effectiveness of QSM over R2* in assessment of parkinson's disease - A systematic review.

The incidence and prevalence of Parkinson's (PD) are increasing rapidly in developing countries. PD is difficult to diagnose based on clinical assessment. Presently, magnetic resonance imaging (MRI) methods such as R2* and Quantitative Susceptibility Mapping (QSM) were found to be useful in diagnosing the PD based on the iron deposition in different regions of the brain. The objective of this review was to evaluate the efficacy of QSM over R2* in assessment of PD. A comprehensive literature search was made on PubMed-Medline, CINAHL, Science Direct, Scopus, Web of Science, and the Cochrane library databases for original research articles published between 2000 and 2018. Original articles that reported the efficacy of QSM and R2* in assessment of PD were included. A total of 327 studies were identified in the literature search. However, only ten studies were eligible for analysis. Of the ten studies, five studies compared the accuracy of QSM over R2* in measuring the iron deposition in different regions of brain in PD. Our review found that QSM has better accuracy in identifying iron deposition in PD patients compared to R2*. However, there is discrepancy in the results between MRI Imaging methods and Postmortem studies. Additional longitudinal research studies are needed to provide a strong evidence base for the use of MRI imaging methods such as R2*and QSM in accurately measuring iron deposition in different regions of brain and serve as biomarkers in PD.

Intracranial iron distribution and quantification in aceruloplasminemia: A case study.

OBJECTIVES: Aceruloplasminemia (ACP) is a rare autosomal recessive disorder characterized by intracranial and visceral iron overload. With R2*-based imaging or quantitative susceptibility mapping (QSM), it is feasible to measure iron in the brain quantitatively, although to date this has not yet been done for patients with ACP. The aim of this study was to provide quantitative iron measurements for each affected brain region in an ACP patient with the potential to do so in all future ACP patients. This may shed light on the link between brain iron metabolism and the territories affected by ceruloplasmin function. METHODS: We imaged a patient with ACP using a 3T magnetic resonance imaging scanner with a fifteen-channel head coil. We manually demarcated gray matter and white matter on the Strategically Acquired Gradient Echo (STAGE) images, and calculated values for susceptibility and R2* in these regions. Correlation analysis was performed between the R2* values and the susceptibility values. RESULTS: Besides the usual territories affected in ACP, we also discovered that the mammillary bodies and the lateral habenulae had significant increases in iron, and the hippocampus was severely affected both in terms of iron content and abnormal tissue signal. We also noted that the iron in the cortical gray matter appeared to be deposited in the inner layers. Moreover, several pathways between the superior colliculus and the pulvinar thalamus, between the caudate and putamen anteriorly and between the caudate and pulvinar thalamus posteriorly were also evident. Finally, R2* correlated strongly with the QSM data (R2 = 0.67, t = 6.78, p < 0.001). CONCLUSION: QSM and R2* have proven to be sensitive and quantitative means by which to measure iron content in the brain. Our findings included several newly noted affected brain regions of iron overload and provided some new aspects of iron metabolism in ACP that may be further applicable to other pathologic conditions. Furthermore, our study may pave the way for assessing efficacy of iron chelation therapy in these patients and for other common iron related neurodegenerative disorders.

Visualization of thalamic calcium influx with quantitative susceptibility mapping as a potential imaging biomarker for repeated mild traumatic brain injury.

A key event in the pathophysiology of traumatic brain injury (TBI) is the influx of substantial amounts of Ca2+ into neurons, particularly in the thalamus. Detection of this calcium influx in vivo would provide a window into the biochemical mechanisms of TBI with potentially significant clinical implications. In the present work, our central hypothesis was that the Ca2+ influx could be imaged in vivo with the relatively recent MRI technique of quantitative susceptibility mapping (QSM). Wistar rats were divided into five groups: naive controls, sham-operated experimental controls, single mild TBI, repeated mild TBI, and single severe TBI. We employed the lateral fluid percussion injury (FPI) model, which replicates clinical TBI without skull fracture, performed 9.4 Tesla MRI with a 3D multi-echo gradient-echo sequence at weeks 1 and 4 post-injury, computed susceptibility maps using V-SHARP and the QUASAR-HEIDI technique, and performed histology. Sham, experimental controls animals, and injured animals did not demonstrate calcifications at 1 week after the injury. At week 4, calcifications were found in the ipsilateral thalamus of 25-50% of animals after a single TBI and 83% of animals after repeated mild TBI. The location and appearance of calcifications on stained sections was consistent with the appearance on the in vivo susceptibility maps (correlation of volumes: r = 0.7). Our findings suggest that persistent calcium deposits represent a primary pathology of repeated injury and that FPI-QSM has the potential to become a sensitive tool for studying pathophysiology related to mild TBI in vivo.

Spatiotemporal variations of magnetic susceptibility in the deep gray matter nuclei from 1 month to 6 years: A quantitative susceptibility mapping study.

BACKGROUND: Quantitative susceptibility mapping (QSM) is emerging as a technique that quantifies the paramagnetic nonheme iron in brain tissue. Brain iron quantification during early development provides insights into the underlying mechanism of brain maturation. PURPOSE: To quantify the spatiotemporal variations of brain iron-related magnetic susceptibility in deep gray matter nuclei during early development by using QSM. STUDY TYPE: Retrospective. SUBJECTS: Eighty-seven infants and children aged 1 month to 6 years. FIELD STRENGTH/SEQUENCE: Enhanced T2 *-weighted angiography using a 3D gradient-echo sequence at 3.0T. ASSESSMENT: QSM was calculated by modified sophisticated harmonic artifact reduction for phase data and sparse linear equations and sparse least squares-based algorithm. Means of susceptibility in deep gray matter nuclei (caudate nucleus, putamen, globus pallidus, thalamus) relative to that in splenium of corpus callosum were measured. STATISTICAL TESTS: Relationships of mean susceptibility with age and referenced iron concentration were tested by Pearson correlation. Differences of mean susceptibility between the selected nuclei in each age group were compared by one-way analysis of variance (ANOVA) and Fisher's Linear Significant Difference (LSD) test. RESULTS: Positive correlations of susceptibility with both referenced iron concentration and age were found (P < 0.0001); particularly, globus pallidus showed the highest correlation with age (correlation coefficient, 0.882; slope, 1.203; P < 0.001) and greatest susceptibility (P < 0.05) among the selected nuclei. DATA CONCLUSION: QSM allows the feasible quantification of iron deposition in deep gray matter nuclei in infants and young children, which exhibited gradual accumulation at different speeds. The fastest and highest iron accumulation was observed in the globus pallidus with increasing age during early development. LEVEL OF EVIDENCE: 4 Technical Efficacy:Stage 2 J. Magn. Reson. Imaging 2018.

Increased iron deposition of deep cerebral gray matter structures in hemodialysis patients: A longitudinal study using quantitative susceptibility mapping.

BACKGROUND: The cerebral iron overload in hemodialysis patients has been reported in a previous study, in which the evaluation of the changes in iron content could be affected by the cross-sectional analysis. PURPOSE: To investigate the longitudinal changes of iron deposition in hemodialysis patients using quantitative susceptibility mapping (QSM) and correlate these findings with the longitudinal changes of neurocognitive function and clinical factors. STUDY TYPE: Prospective; longitudinal. POPULATION: In all, 34 patients and 30 healthy controls (HCs); the mean follow-up interval was 22 ± 7 months. FIELD STRENGTH/SEQUENCE: 3.0T, susceptibility-weighted imaging (SWI). ASSESSMENT: QSM reconstructed from original phase data of SWI was used to measure the susceptibility of gray matter structures including bilateral caudate nucleus (CN), globus pallidus (GP), putmen (PUT), red nucleus (RN), substantia nigra (SN), dentate nucleus (DN), thalamus (THA), pulvinar of thalamus (PT). The Mini-Mental State Examination (MMSE) test and clinical factors were recorded. STATISTICAL TESTING: Analysis of covariance adjusting for age and gender as covariates or a paired t-test for the differences in susceptibility, MMSE scores, and clinical factors among baseline, follow-up patients, and HCs. Correlation and stepwise regression analysis for the relationship between susceptibility, MMSE scores, and clinical factors. RESULTS: The susceptibility of bilateral CN, GP, PUT, RN, SN, DN, THA, PT in follow-up patients was significantly higher than that in baseline between patients and HCs except for left THA (all P < 0.05; Bonferroni corrected). MMSE scores significantly negatively correlated with the susceptibility of bilateral CN, PUT, and RRN in the baseline examination and bilateral CN, PUT, RN, and DN in the follow-up examination (all P < 0.05; false discovery rate [FDR] corrected). The follow-up interval, creatinine, phosphorus, and calcium were independent factors for the increased susceptibility of some nuclei (all P < 0.05). DATA CONCLUSION: The iron deposition of gray matter nuclei in hemodialysis patients increased over roughly a 2-year period and may be a risk factor for neurocognitive impairment. Creatinine and abnormal calcium-phosphorus metabolism were independent risk factors for abnormal iron deposition. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:786-799.